The effects of lupus often leave red, blotchy marks on the surface of the skin.

U of M researchers find gene connected to lupus

Discovery may lead to more individualized treatments for the disease

April 21, 2006

Researchers at the University of Minnesota have identified a
variant of a gene that is present in most people with lupus, a
complex and chronic autoimmune disease.

While some scientists suspect that lupus has genetic elements
because it runs in families, this is the first time research has
shown such a strong link between the presence of a particular gene
variant and a lupus diagnosis.

The research was published online in Nature Genetics on
April 16, 2006.

"As treatments for disease become more personalized and tailored
to an individual's specific situation and genetic makeup,
identifying carriers of this gene variant could be helpful in
developing the most successful treatment plan," said Timothy W.
Behrens, M.D., professor of medicine and co-leader on the
paper.

In addition to the University of Minnesota, the research was
done in partnership with scientists from Uppsala University,
Sweden, and the Broad Institute of Harvard University and the
Massachusetts Institute of Technology.

The researchers studied DNA samples of lupus patients and
healthy people (used as controls) from the United States, Spain,
Sweden, and Argentina, looking for changes in the DNA sequence of a
gene known as interferon regulatory factor 5 (IRF5). They
identified a DNA variant that was found more frequently in lupus
patients compared with the healthy people used as controls. Further
experiments showed that this single change in the DNA sequence of
IRF5 altered the way that the gene is expressed in cells of the
immune system.

Systemic Lupus Erythematosus (SLE) is an inflammatory autoimmune
disease that affects multiple organs. In cases of lupus, a person?s
immune system attacks its own tissues, causing inflammation and
symptoms including pain, fatigue, and rashes. The disease is
difficult to diagnose because it mimics other diseases, making
genetic discoveries like this one promising for developing better
diagnostic tools as well as more effective treatments.

The gene variation Behrens and his colleagues found is
common--50 percent of all people carry one copy of the gene variant
and 25 percent carry two copies. Yet clearly not all people who
carry the gene variant develop lupus. Behrens said this particular
genetic variation is not acting alone to cause the lupus; it likely
interacts with other genes as well as environmental factors to
cause the disease.

The gene the researchers identified plays a role in turning on a
pathway in the body's immune system that is meant to fight
infection. In the case of people with lupus, this pathway is turned
on and it doesn?t turn off, causing the body to begin attacking its
own tissue.

Further study of this gene and how it impacts the body's immune
response could lead to the development of drugs that would target
this pathway to treat patients who carry the gene.

Funding for the research was provided the National Institutes of
Health as well as foundations, including the Lupus Foundation of
Minnesota.